We have discovered a population of New Zealand White rabbit that exhibits behavioral, non-fatal convulsions when given low doses of only psychoactive cannabinoids of marijuana. The available data suggest that these rabbits represent a novel approach to the study of cannabinoids and as such are a potentially unique genetic model of laboratory animal-human correlation for marijuana psychoactivity. The present interdisciplinary research is directed toward developing and characterizing further these unusual animals as a strain-specific paradigm of marijuana action. The overall research objectives are to: (a) develop recognized strains of cannabinoid seizure-susceptible and of non seizure-susceptible rabbits within the same selective inbreeding program, (b) ascertain the locus(i) and mechanisms(s) of action of psychoactive cannabinoids through study of the behavioral genetic, environmental, developmental, and neuropharmacological characteristics and differences of these inbred strains of rabbits. The rabbit strains will be developed by standard selective inbreeding techniques. Genetic, environmental and developmental characters of these rabbits will be delineated by proscribed procedures of selective backcrossing and segregation analyses; resulting generations (F1, F2, etc.) will be statistically evaluated with regards to potential developmental (age sensitivity and maternal-offspring relationships) and environmental (influences of stress, etc.) characters that may underlie behavioral responding following cannabinoid administration. Neuropharmacological studies, (determination of regional brain neurochemical levels) and turn-over (catecholamines, serotonin, amino-acids), detailed electroencephalographic (EEG) analyses, and blood/regional brain uptake and distributions of radiolabeled psychoactive cannabinoids, will also be undertaken in these rabbits. It is anticipated that data derived from this collaborative multidimensional investigation will help to define and characterize this potentially valuable model of cannabinol action as well as to provide relevant and correlative information on the locus(i) and mechanisms(s) of action of marijuana psychoactivity.